As first reported by Bontems, Bull. Sci. Pharmacol. 49: 186-91 (1941), asiatic acid and its trisaccharide asiaticoside can be extracted from Centella asiatica, a small, herbaceous annual, native to the Asian Pacific Rim, which is a member of the carrot and dill family, Apiaceae. The chemical structures of asiatic acid and asiaticoside are shown below:
See Polonsky, Compt. Rend. 232: 1878-80 (1951), and Bull. Soc. Chim. 173-80 (1953).
The management of skin scars and chronic ulcers illustrates known uses for C. asiatica extracts that contain asiatic acid and asiaticoside. In a related vein, the literature also discloses employing C. asiatica extracts in the treatment of skin deformity associated with tuberculosis and leprosy. For example, see Boiteau et al., Bull. Soc. Chim. 31: 46-51 (1949).
For such wound healing, the pharmacological mode of action has been linked to the induction of keratinization, see May, Eur. J. Pharmacol. 4: 331-39 (1968), particularly through promoting skin fibroblast proliferation and synthesis of extracellular matrix components, including collagen I. For instance, see Lu et al., Int'l Dermatol. 43: 801-07 (2004); Skukla et al., J. Ethnopharmacol. 65: 1-11 (1999). According to Bonte et al., Planta Med. 60: 133-35 (1994), a comparison of asiaticoside and acid indicates that the former's sugar moieties seem unnecessary for this biological activity. As discussed in Grimaldi et al., J. Ethnopharmacol. 28: 235-41 (1990), moreover, asiaticoside is completely converted to plasma asiatic acid after oral administration to human subjects.
Knowledge of these wound-healing properties has informed proposals, in U.S. Pat. No. 5,834,437, of dermatological agents that include asiatic acid or one of its derivatives. See also U.S. Pat. No. 6,417,349, which speaks of a palliative effect, in a liver-fibrosis animal model, achieved by peritoneally administering a water-soluble extract of asiaticoside and madecassoside, a related compound also produced by C. asiatica. In addition to wound-healing and anti-fibrotic properties, orally administered asiaticoside has been reported to reduce the levels of spleen cells and inflammatory molecules, including COX-2, PGE2, TNF-alpha, and IL-6, with resultant inhibition or reduction of multiple arthritis parameters, such as paw swelling, arthritis score, and synovial hyperplasia in a standard (collagen-induced) rodent model of arthritis. See Li et al., Yao Xue Xue Bao (Acta Pharma. Sinica) 42: 698-703 (2007).
Although these and other disclosures implicate a therapeutic potential for asiatic acid and asiaticoside, realizing that potential has been hindered by the fact that extracting either compound has proved difficult, with relatively poor yields and low purity. In addition, little is known about producing salts of asiatic acid for use in therapeutic compositions. U.S. Pat. No. 6,891,063 describes certain asiatic acid salts, primarily with an ammonium cation, that are said to be suitable for topical treatment.